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Seven patients with familial amyloid neuropathy (AF amyloidosis) were studied to clarify the pathophysiology of the diarrhea associated with this disorder. Fecal weight and fat determinations, ¹⁴C-glycocholate breath tests, and a test of B₁₂ absorption were performed before and after treatment with co-trimoxazole. Gastric emptying was assessed with conventional roentgen contrast medium and radio-opaque markers. Gastric emptying was delayed, fecal weight and fat excretion increased, and the ¹⁴C-glycholate breath test abnormal in all but one patient. In most cases co-trimoxazole reduced diarrhea, steatorrhea, and ¹⁴C-glycine deconjugation; vitamin B₁₂ absorption returned to normal in one patient after co-trimoxazole treatment. In a jejunal mucosal biopsy specimen, amyloid was absent in the villi, but small deposits were detected along small vessels and nerves in the lamina propria. These findings suggest altered gastrointestinal motility due probably to an autonomic neuropathy which in turn leads to enteral bacterial overgrowth and subsequently to diarrhea and steatorrhea. This diarrhea can be temporarily alleviated by co-trimoxazole treatment.

Xenin, a recently discovered peptide produced by specific endocrine cells of the duodenal mucosa, has shown exocrine, endocrine and motility effects in the gastroenteropancreatic system in animal experiments. The aim of the present investigation was to study the role of xenin in the regulation of duodenojejunal motility of humans. Twenty-nine healthy volunteers from the hospital staff gave informed consent to participate in this investigation. In 20 volunteers, we determined plasma concentrations of immunoreactive xenin at 15 min intervals over a mean time period of 8 h fasting and recorded the interdigestive motor activity of the duodenojejunum. In a double-blind randomized crossover study on other nine subjects, synthetic xenin in a dose of 4 pmol kg-1 min-1 or placebo was infused for 10 min intravenously in the interdigestive period and postprandially after a liquid meal. Duodenojejunal motility was recorded simultaneously. Predefined interdigestive xenin plasma peaks were found to be significantly associated with the phases III of the migrating motor complex. In the interdigestive period, xenin induced a premature phase III activity in each volunteer; this was followed by a second phase III in five out of nine subjects. In the postprandial state, xenin significantly increased contraction frequency and the percentage of aborally propagated contractions. These findings suggest a role of the peptide hormone xenin in modulating interdigestive and postprandial duodenojejunal motility in humans.

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